This proposal and progress report covers the fourth continuing year of this program in the Department of Surgery of the Harvard Medical School at the Peter Bent Brigham Hospital. This is devoted to an understanding of the biologic processes of convalesence and their relationship to bodily changes induced by trauma, injury and surgical operations. Particular concerns include the intermediary metabolism of macronutrients, the nitrogen-sparing effect of carbohydrate and fat, the circulatory effects of hemorrhage and hemodilution, the oxygenation and perfusion of tissues, oxygen transport capacity and tissue acid-base homeostasis as measured by surface cationic electrometry, and the development of computer technology to simplify surgical care. Studies of extracorporeal oxygenation are proceeding, using an extracorporeal pump oxygenator circuit. Studies of the circadian rhythms of biological variables have been intensified. During the past year we have contrasted the circulatory adjustment to normovolemic hemodilution with that seen with the normal transcapillary refill after hemorrhage. With normovolemic hemodilution, cardiac output is grossly increased. Oxygen extraction in the tissues is also increased with a lowering of venous oxygen tension and saturation. During the past year we have also demonstrated increased levels of glucagon and depressed levels of insulin in the serum following major injury and have completed studies of the nitrogen- sparing effect of intravenous carbohydrate and fat in total starvation. Effects on nitrogen intermediary metabolism, levels of glucagon and insulin have been documented. Studies of tissue perfusion using cationic electrometry continue with particular focus on cerebral circulation and muscle metabolism. Studies of circadian rhythms have been extended to the squirrel monkey, an animal ideally adapted to such studies.